Figure 1.

Summary of three osteocalcin null mouse models and their observed phenotypes in different tissues. Karsenty and colleagues generated the first Ocn-deficient mouse (Osc^-/Osc^-) in 1996. Bglap and Bglap2 were deleted in embryonic stem cells using homologous recombination. Diegel and colleagues generated the Bglap and Bglap2 double-knockout (Bglap/2^dko/dko) strain using CRISPR/Cas9-mediated gene editing. Moriishi and colleagues generated the novel Ocn knockout mouse (Ocn ^-/-) using homologous recombination by replacing the genomic region encompassing Bglap and Bglap2 with the neomycin resistant gene. Osc ^-/Osc ^- mice showed increased bone mass and bone formation, while Bglap/2^dko/dko and Ocn ^-/- mice showed similar bone mass/formation compared to their control littermates. Many investigators reported the endocrine role of osteocalcin by studying Osc^-/Osc^- mice. Circulating osteocalcin stimulates β-cell proliferation and insulin synthesis in pancreas. Under-carboxylated osteocalcin may also increase insulin sensitivity in adipose tissue and liver. Elevated osteocalcin increases nutrient uptake in muscle and exercise capacity. In addition, osteocalcin promotes male fertility by increasing testosterone synthesis. However, initial analyses on Bglap/2^dko/dko and Ocn^-/- mice demonstrated that osteocalcin has no effect on glucose level, body fat, muscle weight, and testis size. N/A, not assessed. This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com